Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
  • G01R33/34—Constructional details, e.g. resonators, specially adapted to MR
  • G01R33/34092—RF coils specially adapted for NMR spectrometers
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/30—Sample handling arrangements, e.g. sample cells, spinning mechanisms
  • G01R33/302—Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
  • G01R33/34—Constructional details, e.g. resonators, specially adapted to MR
  • G01R33/34007—Manufacture of RF coils, e.g. using printed circuit board technology; additional hardware for providing mechanical support to the RF coil assembly or to part thereof, e.g. a support for moving the coil assembly relative to the remainder of the MR system
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
  • G01R33/36—Electrical details, e.g. matching or coupling of the coil to the receiver
  • G01R33/3628—Tuning/matching of the transmit/receive coil
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/42—Screening
  • G01R33/422—Screening of the radio frequency field

Definitions

• NMR nuclear magnetic resonance
• High resolution NMR studies are characterized by disposition of a sample on the axis of, and surrounded by the RF coil of the NMR probe at an axial position of excellent homogeneity of the polarizing field.
• a critical aspect of the apparatus is its sensitivity, which is a function of the properties of the RF coil, the temperature, and the geometric relationship of the sample to the interior space of the coil (filling factor).
• a quantitatively high signal amplitude requires a corresponding large quantity of sample, and thus a careful geometric match of sample to the RF coil, yielding a high filling factor, is desired.
• the filling factor is limited by the available transverse interior dimension of the RF coil.
• the aperture (RF window) of the coil determines the effective axial dimension of sample volume, but the physical volume of sample customarily extends beyond the coil aperture in accord with standard practice. Some transverse dimension is inevitably lost to the wall thickness of the sample container and any clearance between sample container and the RF coil, with the result that the volume of sample presented for study is always less than the (available) interior volume of the RF coil. So long as other factors effecting sensitivity have been optimized, maximum sensitivity is reached when the filling factor is maximized. Practical constraints limit maximum filling factor, optimum conditions for NMR studies are understood to include such practically achievable limits.
• the modern NMR probe can accommodate a plurality of coaxial RF coils and each coil is a component of a resonant circuit which is tunable over a range of frequencies and adjustable in impedance match to the corresponding RF source/sink.
• a probe may further contain one or more preamplifier modules to condition received signals.
• Ambient temperature control of the sample and temperature monitoring components are typical features. Controlled high speed rotation of the sample container requires pressurized gas control for levitation of a sample turbine on air bearings, together with a separate pressurized gas control for turbine rotation and rotational rate detector.
• the RF coil (of either superconducting or normal conductor) may utilize temperature control. Consequently, an NMR probe is an expensive and complex instrument.
• micro coil is meant to convey a dimensional scale that is significantly smaller than the dimensions accommodating the standard sample.
• the contemporary standard analytic sample is presented to the probe in a 5 mm o.d. pyrex or quartz tube.
• the micro-coil is most often, a component of a purpose-built probe. It is conventional to present sample for "micro mode" studies in 3 mm. o.d. sample tubes where the micro-coil exhibits a high filling factor to such samples. For the purposes of this work, "micro mode" operations may be so defined in relation to macro studies.
• micro coils In prior art, the use of micro coils is well known and summarized in US patents 5,654,636 and 6,097,188. It is also known to use a micro coil supported on a sample tube as a self-resonant circuit inductively coupled to the fixed RF coil of the NMR probe. See WO2007/020537. Dual use of the same probe for a variety of sample availabilities and requirements for the probe to obtain this benefit are not disclosed therein.
• the present NMR probe (comprising at least one RF resonator) may be unexceptional for studies at resonant frequency coo.
• coo to accommodate inductive coupling to a micro-coil (for samples of substantially limited volume or to achieve enhanced sensitivity) for NMR studies at the same resonant frequency, coo , such circuit must exhibit a tuning range rather more broad than typical of NMR probes.
• the tuning range of the RF resonator circuit, inclusive of the RF coil extends to include a frequency ⁇ c > coo which depends upon the independent operating condition for inductive coupling to a micro-coil containing micro samples
• tuning and matching the probe at coo proceeds in the usual manner.
• the same probe, inclusive of the same RF resonator without modification, may be utilized for examination of micro-samples with the sole addition of a coaxially inserted micro-coil (a much smaller diameter coil surrounding the much smaller sample/sample container.
• the micro-coil comprises a self resonant circuit removable/insertable within the RF resonator.
• the conventional resonator of the probe assembly typically a standard RF coil of the probe
• Figure 1 is a representative probe circuit for this work, including a micro coil.
• Figure 2a is a spectrum of in a conventional 5mm. sample tube within a "5 mm" RF coil.
• Figure 2b is a spectrum of the same sample as figure 2a in a 3mm sample tube supported within a "5 mm" RF coil.
• Figure 2c is a spectrum of the 3mm sample obtained with a micro coil inductively coupled to the "5 mm" coil.
• Figure 3a shows a micro coil enabled sample holder.
• Figure 3b is the insertable micro-sample tube.
• Figure 3c shows the mechanical structure detail of figure 3a.
• Figure 3d is a micro-coil and RF shields mapped onto a plane.
• Figure 4a is a sample holder body for another embodiment.
• Figure 4b is the sample tube for the embodiment of figure 4a.
• Figures 5a, 5b and 5c show another sample holder incorporating a micro-resonant circuit.
• a first RF port 42 communicates with the high frequency (usually proton) channel and is impedance matched thereto through a transmission line matching transformer 44 or the equivalent.
• Inductance 46 inductively couples to the resonant L-C circuit 48 - 49 from the RF source/sink, not shown.
• Capacitive coupling to the RF source/sink is alternatively appropriate.
• Coupling loop 46 is merely an example of coupling to the RF source/sink. (Capacitive coupling may be employed in the alternative).
• the resonant circuit 48-49 is designed to exhibit resonance at ⁇ >o.
• a low frequency (here, deuterium) lock signal is derived through a second RF port 32 with conventional tuning and matching via capacitors 34 and 36.
• the unlabeled inductances represent circuit leads.
• macro mode operation where sample volume is not severely limited, a sample tube 60 is employed, which itself fills the interior volume defined by the resonator coil 48.
• the sample substance fills the sample container to present maximum filling factor.
• this conventional operation is schematically indicated by "A" in figure 1 and may be termed "macro mode" of operation and represents no more than the conventional intended use of the probe.
• the self resonant circuit 50' is capable of insertion within and removal from RF resonator 48 for use with a micro sample, shown schematically by "B" in figure 1 ("micro mode").
• Resonator 48 together with supporting circuit and other probe instrumentalities, is disposed within the probe housing (not shown).
• Resonator 48 is most often an RF coil which may be realized in helical, or saddle coil, or Helmholtz or Alderman-Grant geometries, or as a resonant cavity.
• Self resonant circuit 50' comprises inductance in the form of micro-coil 50 of value L m surrounding the micro sample tube 88 and capacitance C m is furnished largely by the distributed capacitance of the structure of micro-coil 50 and RF shields 98 (figure 3a).
• the micro-coil 50 supported on one surface (interior or exterior) of coil former 52 (not shown), which latter preferably comprises a thin quartz slip glass.
• Electrically floating RF shields 98 are typically disposed on the opposite surface of coil former 52 and supply capacitance to terminals of micro-coil 50, thus forming self resonant circuit 50'.
• the micro-coil 50 is conveniently shown and discussed as providing RF magnetic field B ⁇ transverse to the axial dimension of the coil.
• the circuit 50' is designed to be self-resonant at coo Additional capacitance may be supplied, if required, by a lumped component.
• the tuning range of the (representative) standard probe circuit 40 of figure 1 must have sufficient breadth to include the frequency ⁇ c > coo when the micro-coil 50 is inserted.
• the incremental tuning range depends upon the mutual inductance of the coils 48 and 50 and the dynamic range of tuning capacitor 46.
• An NMR probe having sufficient breadth of tuning (for the same resonator 48) is not the subject of the present work, except as a necessary context of the present work.
• the axis z should not be interpreted as other than a simple geometric axis of the resonator 48. It is understood that the direction of the RF magnetic field direction for resonator 48 may be along z for a solenoidal embodiment of resonator 48 or transverse to z for saddle coil/ Alderman-Grant geometry. The orientation with respect to an external polarizing magnetic field is not to be implied from figure 1.
• Coupling of the resonant circuit 48-49 to the RF source/sink at 50 ohms is achieved conventionally.
• macro mode the micro-coil 50 is absent and the probe circuit 48- 49 is efficiently tuned and matched at ⁇ >o.
• micro mode the self resonant micro-coil circuit 50' inductively couples to the resonator 48 and the circuit 48-49 is re-tuned to ⁇ c and matched to support studies of the micro sample at a>o-
• the parameter ( ⁇ c - coo)/coo is typically larger than encountered in the typical NMR probe.
• NMR probes accommodating studies of both 1 H as well as 13 C, for example, employ different corresponding RF coils for their respective purposes. It is not outside the state of the art to design the circuit 48-49 and supporting components to tune over the range required in the present work (to couple to micro coil 50 resonant at coo) with acceptable match to 50 ohms. It is simply remarked that this is the context for the present work.
• the wide range tuning capability of the resonant circuit 48-49 can be effectuated in another suitable arrangement to accommodate a plurality of frequency-distant resonances using a selectably switchable array of reactances as demonstrated by WO 2005/103749 Al, commonly assigned with the assignee of the present work.
• Another embodiment of the present work includes such an arrangement wherein at least one of the plurality of switched resonant frequencies includes the micro mode frequency corresponding to a macro mode resonance.
• Figure 2b represents a situation where such small volume is sample is studied, but without the benefit of the enhanced sensitivity obtained with a micro coil. It is remarked that in some instances the solvent may contain impurities that interfere with spectral analysis. By concentrating the sample in a smaller volume these impurities present a lesser hindrance to spectral analysis. For the present work, figure 2b is presented for comparison purposes only. [00029] The present work serves diverse studies with a single NMR probe, augmented by the availability of a self resonant micro-coil 50 for use in the small volume mode.
• a self resonant micro-coil 50 is inserted coaxially within resonator 48 to couple to the same 3mm sample tube as employed for figure 2b.
• the micro-coil 50 is of saddle geometry having an RF window length of 12 mm and aligned with the RF aperture of resonator 48.
• the same experiment is repeated again after tuning the standard probe circuit to a value ⁇ c > coo in order to couple to the self resonant circuit 50' at coo. It is apparent that the inductively coupled micro coil experiment of figure 2c yields significantly greater signal (within the smaller RF aperture) for the same mass of sample as observed in figures 2a and 2b.
• the standard tuning specification for the circuit allows about 30 MHz to the lower side of coo (a convenient range inclusive of the fluorine resonance).
• the range of field strength about a nominal design/quoted value is quite small.
• a nominal 500 MHz magnet is specified to present a field strength (measured by proton resonance frequency) in the range 495 to 505, MHz. Consequently, a probe designed for proton studies with a nominal 500 MHz magnet will have a tuning range of at least about 20 MHz to accommodate this tolerance.
• the other major consideration is quite often the frequency separation of two nuclei for which the probe operations are intended. That is quite typically (although not exclusively) 1 H and 19 F, about a 30 MHz separation at 500 MHz.
• a probe designer will build in a tuning range (while maintaining the impedance matching condition) of about 50 MHz for a 1 H and 19 F probe for a nominal 500 MHz spectrometer.
• a broader tuning range is not without precedent, but it is uncommon from the economics of the enterprise.
• Such unusually broad tuning capability is a necessary condition for the dual use benefit of the present work, as may be seen from an analysis of the circuit of figure 1.
• the extended frequency range for inductively coupled resonant tuning is discussed by Kuhns, et al, previously cited.
• the required tuning range need not be assumed to be continuous. It is known to provide for multi- nuclear capability with switchable reactances to establish the desired tuning range centered upon respective discrete resonant frequencies.
• An example is the Auto-X series of NMR probes, commercially available from Varian, Inc, Palo Alto,
• the utility of such prior art is established by identifying these relative discrete capacitances with the gyromagnetic ratio of selected nuclei.
• the present method can be implemented by providing a switchable capacitance to achieve resonance at the discrete center frequency for the respective micro mode operation(s).
• conventional NMR probes often comprise a plurality of RF resonators such as represented by resonator 48.
• a first RF resonator 48 may be coaxially disposed within another RF resonator 48' (not shown) conventionally available for decoupling operations, or the like.
• These conventional RF resonators 48 and 48' will ordinarily be so disposed to exhibit orthogonality of their respective RF magnetic fields.
• the insertion of the micro-coil 50 may be so relatively oriented to obtain maximum inductive coupling to one of the "macro" resonator/coils 48 or 48' with minimal inductive coupling to the other coil 48' or 48.
• the conventional probe comprises a single, or plural resonators, it is an important requirement that the micro-coil 50 take on a desired azimuthal orientation of its RF magnetic field with respect to that of one RF resonator 48 (or the other, of plural resonators).
• Mechanical support of the micro-coil 50 is preferably independent of the support of the micro-sample container.
• An exemplary embodiment is shown in figures 3a, 3b, 3c and 3d.
• the micro-coil axis is coaxial with that of the coil 48. It is understood that the resonators 48, 48' are fixed in respect of the NMR probe housing and represent conventional structure.
• the micro-coil is directly supported on the outer surface of former 94, in turn suspended from bushing 96.
• An outer tube 95' is shown as typically employed for the confinement of an axially directed heating gas passing over the sample region for temperature regulation.
• the probe bushing 96 is recognized by those of skill in the art as the mechanical equivalent of a spinner body, or turbine, for conventional sample spinning and/or for simply securing and aligning a sample container on the axis of a probe coil.
• the probe bushing 96 is, more generally an alignment bushing that (in a preferred embodiment) supports a micro-coil 50 and secures coaxial alignment of micro-coil 50 and the sample container 88 with respect to the probe housing.
• the probe bushing 96 is readily insert- able and removable from the housing of the probe to facilitate transition between conventional utilization of the probe (macro mode operation).
• the sample container is similarly readily insert-able and removable from the probe bushing 96.
• the probe bushing 96 When inserted in the probe housing, the probe bushing 96 conveniently is supported by the (conventional provided) cup shaped air bearing base, or equivalent surface, of such conventional arrangement of the probe housing in order to secure axial alignment of the probe bushing 96 with the fixed resonator(s) 48-48'.
• the micro-coil 50 In micro-coil operation, it is understood that the micro-coil 50 is arranged to orient the B 1 field direction of the micro-coil to a desired azimuthal direction.
• Figure 3b illustrates the sample insertion assembly which provides for the insertion/removal of a micro-sample container 88 independently of the micro-coil 50.
• a sample bushing 80 is received in a conformal cavity on the upper surface of probe bushing 96 to obtain the appropriate coaxial alignment of the sample container with the resonator 48.
• the sample container is a cylindrical tube and therefore requires no particular azimuthal orientation for a cylindrical cross section sample container.
• the sample container may take on other cross sectional forms as disclosed in US patent 6,917,201, and US patent 7,557,578. In such cases, the sample insertion subassembly resembles that shown in figure 4b in order to obtain the desired azimuthal alignment with respect to the RF magnetic field directions of resonator 48 and micro-coil 50.
• Floating RF shields 98 are supported on an inner surface of the former 94 (by way of example) and serve the dual purpose of defining the RF (B 1 ) aperture, or window, for the micro-coil 50 and also providing the capacitance of the self resonant micro-coil circuit.
• Floating shields deployed for this purpose are well known. See US patent 6,008,650, commonly assigned herewith. In fig. 3D a micro-coil 50 is shown in a planar mapping with RF shields 98 (the latter displaced from the coil by thickness of coil former 94).
• the micro-coil 50 is supported on a separate former 86 in turn supported on the outer surface of the micro sample container 88. It is well known to formulate the requisite materials to maintain magnetic homogeneity of the space by magnetic susceptibility matching of such materials to the magnetic environment.
• the micro-coil 50 is preferably supported on a thin-walled sleeve 86 of fused silica or the like, which in turn, is directly supported on the micro sample container 88.
• the inner surface of the fused silica sleeve 86 supports the floating RF shields (shown as 98 in figure 3c) which define the RF aperture for irradiation of sample and supply capacitance to the micro-coil self resonant circuit 50'.
• the micro-coil 50 and the shields 87 may be integral with the sleeve 86 using common deposition techniques.
• the sleeve is of sufficient length to extend well beyond the sensitive region of the NMR instrument, (well beyond the RF apertures of the resonator 48, 48' and micro-coil 50) where an appropriate adhesive, or equivalent, may be applied to secure the axial position of the micro-coil 50.
• the micro-sample tube orientation bushing 80 may secure a desired orientation via radial orientation pin 82 received into a slot 82' in the top surface of probe bushing 96'.
• self-resonant circuit 50' is inserted/removed together as a unit with the micro sample container 88.
• FIG. 4a, 4b, Figure 5a, 5b, and 5c feature the incorporation of the micro-coil 50 as integral to the (micro) sample container 88.
• the micro-coil 50 is preferably deposited directly on the outer surface of the micro sample container 88, obviating the need for a separate coil former.
• the capacitance 53 completing the self resonant circuit 50' is supplied at some remove from the active region of the micro- coil 50. This is shown schematically in Figure 5b where the capacitance is supplied from chip capacitors or from specially constructed distributed capacitance. As shown, the floating RF shields of the previously discussed embodiments are here omitted.
• a resonator 48 or the micro-coil 50 The RF magnetic field directions of the respective coils (48, 50) may be orthogonal (as desired for indirect detection and like experiments where a second probe coil 48' is available for excitation).
• the RF resonator should be coaxial for maximum coupling between non-solenoidal coils (48, 48', 50).
• Coaxial coils (48, 48' and 50) take the form of saddle coils, birdcage coils, and the like, where the RF magnetic field is transverse to the geometric axis of the coil which most often coincides with the bore of the polarizing magnet of the NMR instrument.
• Solenoidal coils for which the RF magnetic field direction coincides with the geometric axis, are less common, but may be employed as one or another of the coils used in the present work.
• the RF resonator 48 may also take the form of a resonant cavity.
• the coaxial property facilitates insertion and removal of the micro-coil 50.
• the relative orientations of the external polarizing field, and the respective RF magnetic field directions B 1 , B 1 ' of the resonator (48, 48') and the RF field B ⁇ of micro-coil 50 are critical to the particular NMR experiment.

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• 2009
  • 2009-07-31 US US12/534,060 patent/US8063639B2/en not_active Expired - Fee Related
• 2010
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  • 2010-07-29 EP EP10805071A patent/EP2459993A2/en not_active Withdrawn
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